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Free keywords:
Adolescent
Adult
Aged
Base Sequence
Carcinoid Tumor/*genetics/pathology
Chromatin Assembly and Disassembly/*genetics
Chromosome Mapping
DNA Copy Number Variations
Exome/genetics
Female
Gene Dosage
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome, Human/genetics
Humans
Lung Neoplasms/*genetics/pathology
Male
Middle Aged
Molecular Sequence Data
*Mutation
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
Young Adult
Abstract:
Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids.
